ArticleNPJ precision oncology2018
Transcriptomic analysis of hepatocellular carcinoma reveals molecular features of disease progression and tumor immune biology.
Article in NPJ precision oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Inhibition of PERK signaling suppresses tumor progression and blocks GP73-GRP78-dependent stromal activation in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2026Article
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Tumor Immune Contexture Model Predicts Prognosis and Immunotherapy Response in Gastric Cancer.The journal of gene medicine · 2025Article
- Joint Transcriptomic Analysis of the Effect of Iron Concentration on Piglet Liver and Functional Validation of Iron Regulatory Genes.Current issues in molecular biology · 2025Article
- Serum fibrosis marker M2BPGi-based novel score predicts survival of unresectable HCC undergoing immunotherapy.JHEP reports : innovation in hepatology · 2025Article
- State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Hedgehog components are overexpressed in a series of liver cancer cases.Scientific reports · 2024Article
- Unveiling the Role of Mechanical Microenvironment in Hepatocellular Carcinoma: Molecular Mechanisms and Implications for Therapeutic Strategies.International journal of biological sciences · 2024Review
- A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors.Human cell · 2023Article
- A decade of liver organoids: Advances in disease modeling.Clinical and molecular hepatology · 2023Review
- A Paradigm Shift in Primary Liver Cancer Therapy Utilizing Genomics, Molecular Biomarkers, and Artificial Intelligence.Cancers · 2023Review
- Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment.Scientific reports · 2023Article
- Transcriptome analysis creates a new era of precision medicine for managing recurrent hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix.Frontiers in immunology · 2023Review
- Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials.Bioengineering (Basel, Switzerland) · 2022Review
- Fibrotic activity quantified in serum by measurements of type III collagen pro-peptides can be used for prognosis across different solid tumor types.Cellular and molecular life sciences : CMLS · 2022Review
- Hemojuvelin deficiency promotes liver mitochondrial dysfunction and predisposes mice to hepatocellular carcinoma.Communications biology · 2022Article
- Targets of immunotherapy for hepatocellular carcinoma: An update.World journal of hepatology · 2022Review
- A Novel TAF-Related Signature Based on ECM Remodeling Genes Predicts Glioma Prognosis.Frontiers in oncology · 2022Article
- Molecular classification of hepatocellular carcinoma: prognostic importance and clinical applications.Journal of cancer research and clinical oncology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) develops in the context of chronic inflammatory liver disease and has an extremely poor prognosis. An immunosuppressive tumor microenvironment may contribute to therapeutic failure in metastatic HCC. Here, we identified unique molecular signatures pertaining to HCC disease progression and tumor immunity by analyzing genome-wide RNA-Seq data derived from HCC patient tumors and non-tumor cirrhotic tissues. Unsupervised clustering of gene expression data revealed a gradual suppression of local tumor immunity that coincided with disease progression, indicating an increasingly immunosuppressive tumor environment during HCC disease advancement. IHC examination of the spatial distribution of CD8+ T cells in tumors revealed distinct intra- and peri-tumoral subsets. Differential gene expression analysis revealed an 85-gene signature that was significantly upregulated in the peri-tumoral CD8+ T cell-excluded tumors. Notably, this signature was highly enriched with components of underlying extracellular matrix, fibrosis, and epithelial-mesenchymal transition (EMT). Further analysis condensed this signature to a core set of 23 genes that are associated with CD8+ T cell localization, and were prospectively validated in an independent cohort of HCC specimens. These findings suggest a potential association between elevated fibrosis, possibly modulated by TGF-β, PDGFR, SHH or Notch pathway, and the T cell-excluded immune phenotype. Indeed, targeting fibrosis using a TGF-β neutralizing antibody in the STAM™ model of murine HCC, we found that ameliorating the fibrotic environment could facilitate redistribution of CD8+ lymphocytes into tumors. Our results provide a strong rationale for utilizing immunotherapies in HCC earlier during treatment, potentially in combination with anti-fibrotic therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.